Project Abstract People with type 2 diabetes mellitus have an increased risk of developing cardiovascular disease compared to people without diabetes. This increased risk persists even though people with diabetes derive relatively greater benefit from blood pressure lowering, lipid control and aspirin use than do non-diabetic individuals. It follows from this that there are other atherogenic mechanisms, not addressed by current modalities of cardiovascular prevention, present in people with diabetes. Amelioration of these "other factors" could lead to lower cardiovascular disease risk. One plausible "other factor" is excessive redox imbalance, defined as the excess formation or insufficient removal of reactive oxygen, nitrogen and carbon molecules. People with diabetes have elevated oxidative, carbonyl and nitrosative stress. These processes are linked to the initiation and propagation of atherosclerosis. Nuclear factor kappa beta (NF-kB) is a gene which plays an important role in the control of inflammation and redox imbalance. Recent laboratory studies show that salsalate - a medication used for many years for the treatment of arthritic conditions - can block the activation of NF-kB. This finding suggests that salsalate may be a novel treatment approach for the management of DM. The Targeting Inflammation Using Salsalate in Type 2 Diabetes (TINSAL T2D) study examines the use of salsalate as a new paradigm of therapy for the treatment of DM. Its primary goal is to test whether the inhibition of NF- kB activity results in lower blood glucose levels in people with diabetes. Its seconday outcome is to examine whether blockade of NF-kB results in lower levels of inflammation and vascular factors implicated in atherogenesus. The present sub-study seeks to gain understanding of the impact of salsalate therapy for the treatment of DM by examining its effect on carbonyl, oxidative and nitrosative stress. These latter factors are believed to play an important role in the vascular complications of DM. Current medical therapy for the prevention of diabetic complications does not address the amelioration of these factors. Lowering redox imbalance with salsalate therapy may play an important role in the prevention of diabetic vascular complications. PUBLIC HEALTH RELEVANCE: Project Narrative This study will test the use of salsalate, a form of aspirin, for people with diabetes. If effective, this treatment could reduce the risk of heart attacks and strokes that frequently occur in people with diabetes.